What Are Ozanimod and Siponimod?

Ozanimod (marketed as Zeposia) and siponimod (marketed as Mayzent) belong to a class of medications called sphingosine 1-phosphate (S1P) receptor modulators. These oral medications work by preventing certain immune cells from leaving lymph nodes, which reduces the number of cells available to cause inflammation and damage to the central nervous system in multiple sclerosis.

Both medications are relatively new additions to the MS treatment landscape. Ozanimod received FDA approval in 2020 for treating relapsing forms of MS, including clinically isolated syndrome, relapsing-remitting MS, and active secondary progressive MS. Siponimod was approved in 2019 specifically for active secondary progressive MS and relapsing forms of the disease. While they share a common mechanism of action, their specific receptor selectivity and pharmacological properties differ significantly.

Mechanism of Action Differences

The primary distinction between ozanimod and siponimod lies in their receptor selectivity. Ozanimod selectively targets S1P1 and S1P5 receptors, whereas siponimod binds to S1P1, S1P5, and to a lesser extent, S1P3, S1P2, and S1P4 receptors. This difference in selectivity influences their side effect profiles and monitoring requirements.

Ozanimod's higher selectivity for S1P1 and S1P5 receptors may result in fewer cardiac effects compared to less selective S1P modulators. Siponimod's broader receptor binding profile may contribute to its effectiveness in secondary progressive MS but may also increase the potential for certain side effects. Both medications ultimately prevent lymphocytes from leaving lymph nodes, reducing the inflammatory attack on myelin in the central nervous system, but through slightly different molecular pathways.

Clinical Efficacy Comparison

Clinical trials have demonstrated the efficacy of both medications, though direct head-to-head studies comparing ozanimod and siponimod have not been conducted. The SUNBEAM and RADIANCE trials showed that ozanimod reduced annualized relapse rates by approximately 38% compared to interferon beta-1a. Additionally, ozanimod showed benefits in reducing new or enlarging brain lesions on MRI and slowing brain volume loss.

Siponimod was evaluated in the EXPAND trial, which focused on secondary progressive MS patients. The study demonstrated that siponimod reduced the risk of disability progression by about 21% compared to placebo. It also showed benefits in reducing annualized relapse rates and new MRI lesions. Siponimod is notable for being one of the few therapies specifically tested in and approved for secondary progressive MS, while ozanimod's approval for this indication was based on its effectiveness in relapsing forms of MS.

When considering efficacy, it's important to note that the patient populations in these trials differed somewhat, making direct comparison challenging. The choice between medications often depends on the specific type and stage of MS as well as individual patient factors.

Safety Profile and Monitoring Requirements

Both medications require specific monitoring protocols, but with notable differences. Before starting Zeposia (ozanimod), patients need baseline assessments including blood tests, ECG, and ophthalmic evaluation. However, ozanimod does not require genetic testing or a first-dose observation period in most patients, which can be more convenient.

In contrast, Mayzent (siponimod) requires CYP2C9 genotype testing before initiation, as genetic variations affect how the drug is metabolized. Patients with certain genotypes may require lower doses or may not be candidates for siponimod. Additionally, siponimod typically requires first-dose monitoring for cardiac effects in certain patient populations.

Both medications can cause transient heart rate decreases and potential liver enzyme elevations. Common side effects for both include upper respiratory infections, headache, and elevated liver enzymes. Siponimod may have a slightly higher incidence of hypertension, while ozanimod has been associated with more frequent reports of upper respiratory tract infections in some studies. Neither medication requires routine laboratory monitoring after treatment initiation, unlike some other MS therapies.

Practical Considerations for Patients

Several practical factors may influence the choice between ozanimod and siponimod. Ozanimod is taken as a 0.92 mg capsule once daily, with an initial dose escalation over the first week. Siponimod dosing depends on the CYP2C9 genotype, with most patients taking 2 mg tablets daily after a 5-day titration period.

Insurance coverage and out-of-pocket costs vary widely between patients. Both Bristol Myers Squibb (manufacturer of Zeposia) and Novartis (manufacturer of Mayzent) offer patient assistance programs that may help reduce costs for eligible patients.

Pregnancy considerations also differ between the medications. Both drugs should be discontinued before planned pregnancies, but ozanimod requires a 3-month washout period before conception attempts, while siponimod requires a 10-day washout period. Women of childbearing potential should use effective contraception during treatment with either medication and for a period after discontinuation.

Conclusion

When choosing between ozanimod and siponimod, patients and healthcare providers should consider the specific type and stage of MS, comorbidities, monitoring preferences, and practical aspects like insurance coverage. Both medications represent significant advances in MS treatment with their oral administration and effectiveness in reducing relapses and disease progression. The decision ultimately depends on individual patient factors and should involve thorough discussion with healthcare providers who can weigh the benefits and risks in each specific case. As the understanding of these medications continues to evolve with real-world experience, their optimal place in MS treatment algorithms may become even clearer.

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This content was written by AI and reviewed by a human for quality and compliance.